Two oral presentations highlight first-in-class Thumb-1 polymerase inhibitor with single-agent broad-spectrum efficacy against influenza, RSV, SARS-CoV-2, HCV, HBV and HDV
SAN DIEGO — Model Medicines, an AI-first biotechnology company developing first-in-class therapeutics, today announced that it will be presenting two abstracts at the Congress of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID Global 2026) in Munich, Germany. Both presentations will be delivered by Daniel Haders, PhD, Founder and Chief Executive Officer of Model Medicines, on April 18, 2026. The data advance MDL-001 toward two first-in-class therapeutic goals: a universal direct-acting antiviral for influenza-like illness (Influenza, RSV, and Coronavirus) and a universal direct-acting antiviral for chronic hepatitis (Hepatitis C, Hepatitis B, and Hepatitis D).
ESCMID Oral Presentations
Presentation 1: Universal Direct-Acting Antiviral For Influenza-Like Illness
Title: MDL-001, an oral direct-acting Thumb-1 polymerase inhibitor, demonstrates broad-spectrum activity against influenza viruses, respiratory syncytial virus, and SARS-CoV-2 with oral proof-of-concept
Session: OS002 — Three viruses, one winter: what we miss, what we treat, what comes next
Date: April 18, 2026
Location: Hall A1-3
Abstract: 5803
Authors: V. Woods, T. Umansky, S. Russell, A. Goodman, M. Bobardt, B. McGovern, M. Rodriguez, A. García-Sastre, K. White, W. Brubaker, P. Gallay, D. Smith, D. Haders
Presentation 2: Universal Direct-Acting Antiviral For Chronic Hepatitis
Title: MDL-001, an oral direct-acting Thumb-1 polymerase inhibitor, demonstrates single-agent efficacy against HCV/HBV co-infection in vitro, and achieves HCV and HBV preclinical proof-of-concept
Session: EF005 — Old viruses, new weapons: emerging antiviral therapies from bench to bedside
Date: April 18, 2026
Location: Arena 2
Abstract: 5778
Authors: V. Woods, T. Umansky, S. Russell, A. Goodman, M. Bobardt, W. Brubaker, P. Gallay, D. Smith, D. Haders
There are currently no single agent antivirals approved to treat the annual convergence of the acute respiratory tripledemic viruses: influenza, RSV, and SARS-CoV-2. In chronic hepatitis, the FDA maintains black box warnings on all HCV direct-acting antiviral (DAA) regimens due to the risk of HBV reactivation in co-infected patients. Both of these clinical voids underscore the high unmet medical need for a single agent with broad-spectrum, direct acting antiviral activity.
MDL-001’s demonstrated activity across both acute respiratory and chronic hepatic viral infections, combined oral bioavailability, favorable pharmacokinetics, and demonstrated safety positions the compound as a potential first-in-class therapy that could meaningfully improve multiple treatment paradigms.
“The development of a direct-acting broad-spectrum non-nucleoside antiviral has been considered impossible,” said Daniel Haders, PhD, Founder and CEO of Model Medicines. “The conventional wisdom held that allosteric sites on viral polymerases are too poorly conserved for cross-family targeting. Our work demonstrates that the RdRp Thumb-1 pocket is conserved across viral families. We believe this target will give rise to successive generations of best-in-class therapeutics. These ESCMID presentations reflect the depth of the preclinical evidence supporting both programs.”
ESCMID Global 2026 convenes in Munich, Germany, from April 17–21, 2026. Abstract details are available through the ESCMID Abstract Finder.
About the Target: RdRp Thumb-1, A Conserved and
Druggable Allosteric Target Conventional
scientific wisdom holds that allosteric sites on viral polymerases diverge too
rapidly to enable broad-spectrum Direct Acting Antiviral (DAA) development. Model Medicines
overturned this assumption by demonstrating the structural conservation of the
RNA-dependent RNA polymerase (RdRp) Thumb-1 allosteric pocket across viral
families. The Thumb-1 site governs an essential mechanism for viral
replication. The Thumb-1 pocket interacts with the viral Λ1-loop to control an
indispensable conformational change required for polymerase initiation. Viruses
cannot abandon this mechanism without sacrificing their replicative fitness.
This target discovery is the biological foundation for the Model Medicines’
Virology Program. About MDL-001:
Discovery and Preclinical Profile Model Medicines
utilized its AI-driven GALILEOTM platform to discover novel
broad-spectrum inhibitor chemistry for this target within a multi-scaffold
Markush structure. The research team trained GALILEOTM on a
proprietary dataset spanning multiple viral families. This training enabled the
model to learn the structural and chemical features required for broad-spectrum
Thumb-1 inhibition. A library of
potent inhibitors has been discovered, reduced to practice and validated.
Specifically, MDL-001 is the first DAA shown to be potent against multiple
viral families in vitro: Orthomyxoviridae, Pneumoviridae, Coronaviridae,
Flaviviridae, Komioviridae, and Hepadnaviridae. MDL-001 has demonstrated
multi-log antiviral efficacy against Influenza, SARS-CoV-2, HCV and HBV in
animal models. Furthermore, in vivo results demonstrate superiority or
equivalence to multiple standards of care, including sofosbuvir, oseltamivir,
remdesivir, and nirmatrelvir. Model Medicines
virology program, the discovery of the RdRp Thumb-1 site, and MDL-001 preclinical
Proof-of-Concept data has been peer reviewed, accepted and presented at IDWeek
2025[1],
AASLD 2025[2], HepDART 2025, and CROI 2026[3].
The company will present further data at ESCMID 2026[4],[5].
The full preclinical data readout can be found here. Model Medicines plans to
file an Investigational New Drug (IND) application with the FDA for MDL-001 in
late 2026 and anticipates commencing clinical trials in 2027.
About Model Medicines. Model Medicines is an AI-first
biotechnology company engineering first-in-class small molecules that target
the biological linchpins underlying disease. The company’s research spans
infectious disease, oncology, and inflammation, with programs designed around
conserved molecular choke points that drive multiple pathologies. Model
Medicines has discovered a direct-acting, non-nucleoside, broad-spectrum
antiviral (MDL-001) and a potent, selective and novel BRD4 inhibitor
(MDL-4102). Its work demonstrates how large-scale computation can uncover
entirely new classes of drugs once thought unreachable. Model Medicines is
advancing a new generation of therapeutics that redefine what is possible in modern
drug discovery. Learn more at www.modelmedicines.com
Media Contact: Patrick O’Neill Head of Partnerships &
Investor Relations media@modelmedicines.com www.modelmedicines.com
[1] MDL-001: A Broad-Spectrum Antiviral Targeting the Thumb-1 Domain of Viral Polymerases, Open Forum Infectious Diseases, Volume 13, Issue Supplement_1, January 2026, ofaf695.084, https://doi.org/10.1093/ofid/ofaf695.084
[2] MDL-001 As A Next Generation Hcv Thumb-1 inhibitor With Clinical-Stage Safety, The Liver Meeting: 2025 Abstracts. (2025). Hepatology (Baltimore, Md.), 82(S1), S1–S2308. https://doi.org/10.1097/HEP.0000000000001493
[3] MDL-001, a novel oral thumb-1 polymerase inhibitor, shows efficacy in HCV/HBV in vitro and in vivo. Paper presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 22-25, 2026; Denver, CO. Abstract 589. https://www.croiconference.org/abstract/2417-2026/
[4] MDL-001, an oral direct-acting Thumb-1 polymerase inhibitor, demonstrates single-agent efficacy against HCV/HBV co-infection in vitro, and achieves HCV and HBV preclinical proof-of-concept. Abstract presented at: ESCMID Global 2026; April 18, 2026; Munich, Germany. Abstract 5778.
[5] MDL-001, an oral direct-acting Thumb-1 polymerase inhibitor, demonstrates broad-spectrum activity against influenza viruses, respiratory syncytial virus, and SARS-CoV-2 with oral proof-of-concept in mice. Abstract presented at: ESCMID Global 2026; April 18, 2026; Munich, Germany. Abstract 5803.
